Real-time label-free quantitative monitoring of biomolecules without surface binding by floating-gate complementary metal-oxide semiconductor sensor array integrated with readout circuitry

Kim, Seong‐Jin; Yoo, Kicheon; Shim, Jeoyoung; Chung, Wonseok; Ko, Cheng−Hao; Im, Maesoon; Kim, Lee Sup; Yoon, Euisik

doi:10.1063/1.2803848

Cited by 3 publications

(1 citation statement)

References 16 publications

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“…However, there is a need to improve the repeatability, reliability and sensitivity of the arrays by improving the functionalization of the gate surfaces. This is usually done on metal oxide layers, thermal SiO 2 (1,2,4,5,(17)(18)(19), oxidized Al (Al 2 O 3 ) (16,20), or low-pressure chemical vapor deposited (LPCVD) Si nitride surfaces (6). The gates must be functionalized so as to passivate any proton binding sites since these can bind or release protons, counteracting the potential changes generated by the DNA attachment (21,22,10).…”

Section: Introductionmentioning

confidence: 99%

Hafnium Silicate Gate Insulators in Field Effect Sensors Used to Detect DNA Hybridization

et al. 2008

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The detection of DNA hybridization using fieldeffect transistors (BioFETs) has attracted attention recently [1]. A model has been developed [2-3] to estimate threshold voltage shifts obtained from the current-voltage characteristics both before and after probe attachment and after hybridization with the targets. SiO 2 or gold surfaces are usually used on the floating gates. High-k dielectric materials, e.g. HfO 2 or HfSiO x , may improve the performance of the BioFETs if they can be more effectively passivated and functionalized than SiO 2 [4]. In this paper, we will report the fabrication of BioFET sensors with HfSiO x gate insulators which do not suffer from parasitic leakage effects in solution which result from the crystallization of HfO 2 . Results showing the direct electronic detection of surface functionalization, DNA attachment, and hybridization on the gate surface will be described and compared with estimates from the model.The fabrication of the BioFETs followed standard MOS fabrication processes. HfSiO x film was grown on top of 80 Ǻ thermal oxide by atomic layer deposition and MOS compatible post-processes were applied to expose the gate insulator after device fabrication. The processed chips were wire-bonded to a header and polydimethylsiloxane rings were attached to contain the phosphate-buffered saline electrolytes during the measurements.The pH sensitivity was measured before and after the HfSiO x gate was functionalized with Glycidoxypropyl trimethoxysilane (GPTMS) vapor. After functionalization, the sensitivity decreased from 31.4 mV/pH to 24.6 mV/pH due to the passivation of some of the O-H bonds on the HfSiO x surface by GPTMS. Fig. 1 shows the BioFET threshold shift due to a change in electrolyte concentration from 0.015 M to 0.3 M before DNA probes were immobilized onto the surface. The large initial negative transient is caused by a temporary change in the surface pH due to the establishment of a diffusion potential in the well. After mixing and flushing, this signal is reduced, resulting in a small net shift in the threshold voltage which was partially compensated by the initial drift of the Ag/AgCl micro-reference electrode. After the amine-modified 34 mer ssDNA probe molecules (concatenated 17 mer sequence) were attached to the surface in 0.3 M buffer, the buffer solution concentration was reduced, and then cycled from 0.015 M to 0.3 M. A significant threshold voltage change of 33 mV was observed in Fig. 2(a) as a result of the concentration change, indicating that the BioFET is very sensitive to the probe molecules. Fig. 2(b) shows the threshold voltage changes after 17 mer complementary DNA target molecules were applied; the hybridization caused a net increase in the threshold voltage shift of 3mV, which is comparable to the result from BioFETs with SiO 2 gate insulators. Noncomplementary targets produced no net shift.The model shows that a larger hybridization signal is expected when more O-H bonds are passivated by surface functionalization and / or the probe DNA molecule density ...

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Section: Introductionmentioning

confidence: 99%

Hafnium Silicate Gate Insulators in Field Effect Sensors Used to Detect DNA Hybridization

et al. 2008

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Low-power circuit challenges in cellular/molecular interfaces

Yoon

2010

2010 International Electron Devices Meeting

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Label-Free CMOS Bio Sensor With On-Chip Noise Reduction Scheme for Real-Time Quantitative Monitoring of Biomolecules

Kim

Yoon

2012

IEEE Trans. Biomed. Circuits Syst.

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We present a label-free CMOS field-effect transistor sensing array to detect the surface potential change affected by the negative charge in DNA molecules for real-time monitoring and quantification. The proposed CMOS bio sensor includes a new sensing pixel architecture implemented with correlated double sampling for reducing offset fixed pattern noise and 1/f noise of the sensing devices. We incorporated non-surface binding detection which allows real-time continuous monitoring of DNA concentrations without immobilizing them on the sensing surface. Various concentrations of 19-bp oligonucleotides solution can be discriminated using the prototype device fabricated in 1- μm double-poly double-metal standard CMOS process. The detection limit was measured as 1.1 ng/μl with a dynamic range of 40 dB and the transient response time was measured less than 20 seconds.

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Real-time label-free quantitative monitoring of biomolecules without surface binding by floating-gate complementary metal-oxide semiconductor sensor array integrated with readout circuitry

Cited by 3 publications

References 16 publications

Hafnium Silicate Gate Insulators in Field Effect Sensors Used to Detect DNA Hybridization

Hafnium Silicate Gate Insulators in Field Effect Sensors Used to Detect DNA Hybridization

Low-power circuit challenges in cellular/molecular interfaces

Label-Free CMOS Bio Sensor With On-Chip Noise Reduction Scheme for Real-Time Quantitative Monitoring of Biomolecules

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